Viral tools for studying NG2 cells

用于研究 NG2 细胞的病毒工具

• 批准号: 8537790
• 负责人: Shaoyu Ge
• 金额: $ 18.17万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-04 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8537790
• 关键词: Adult; Biochemical; Brain; CSPG4 gene; Cell Lineage; Cell physiology; Cell surface; Cells; Chondroitin Sulfate Proteoglycan; Communities; Demyelinations; Deposition; Development; Differentiation Antigens; Genes; Goals; Homeostasis; Injury; Life; Location; Mus; Myelin; NG2 antigen; Neuroglia; Neurons; Oligodendroglia; Paper; Peripheral Nervous System; Plasmids; Population; Proliferating; Property; Proteins; Publishing; RNA Interference; Retroviral Vector; Retroviridae; Rodent; Role; Site; Slice; Spinal Cord; Spinal cord injury; Stem cells; Subfamily lentivirinae; Synapses; Viral; Viral Vector; Virus; base; cell type; electrical property; in vivo; injured; mature animal; mutant; novel; oligodendrocyte precursor; optogenetics; precursor cell; repository; response; tool; vector

DESCRIPTION (provided by applicant): Oligodendrocytes, the myelin forming cells of the CNS, develop from identified precursor cells known alternately as oligodendrocyte progenitor cells (OPCs), polydendrocytes, or NG2 cells. These cells appear about midgestation in rodents at specific locations within the developing CNS, migrate extensively, proliferate as they migrate, and then slowly differentiate into myelin-forming cells. Surprisingly, a large fraction of the OPC population fails to fully differentiate and persists throughout the adult CNS as a slowly dividing cell that can be considered an fourth glial cell type. The functions of these adult OPCs are not well understood, in part, because of their unusual mixture of glial and neuronal properties. Major questions remain regarding 1) the phenotypic plasticity of these cells in developing and adult animals and after injury and 2) the role of electrical excitability in OPC development and function. The goal of this proposal is to develop new viral-based tools for analyzing the development and properties of NG2+ OPCs. Our strategy takes advantage of the availability of cell-type specific inducible cre mouse driver lines and recently developed "flip" vectors in which tandem mutant loxP sites allow for inversion of selected genes from an anti-sense to sense orientation. This strategy allows for temporal control of the expression of marker antigens, functional proteins and RNAi. The tools to be developed here can be used widely to study other glial cell types within the central and peripheral nervous system.

描述（由申请人提供）：少突胶质细胞，CNS的髓磷脂形成细胞，由已鉴定的前体细胞或称为少突胶质细胞祖细胞（OPC），多胶质细胞或NG2细胞形成。这些细胞出现在发育中心的特定位置中的啮齿动物中的中间化，广泛迁移，随着迁移而增殖，然后慢慢区分髓磷脂形成细胞。令人惊讶的是，很大一部分OPC种群无法完全区分整个成年CNS，作为一个缓慢的分裂细胞，可以被视为第四层神经胶质细胞类型。这些成年OPC的功能并没有得到很好的理解，部分原因是它们具有神经胶质和神经元特性的异常混合物。关于1）这些细胞在发育和成年动物以及受伤后以及2）电兴奋性在OPC开发和功能中的作用的主要问题。该提案的目的是开发新的基于病毒的工具来分析NG2+ OPC的开发和特性。我们的策略利用了细胞类型的特定诱导CRE小鼠驱动线的可用性，并最近开发了“翻转”向量，其中串联突变型LOXP位点允许将所选基因从反义转移到感觉方向。该策略允许对标记抗原，功能蛋白和RNAi的表达时间控制。这里要开发的工具可广泛用于研究中央和周围神经系统中的其他神经胶质细胞类型。